It's all a matter of how much dinero you want to blow... Let's assume first that a) you want to improve things but don't want to drop many thousands just yet, and b) a room that size would benefit from a bigger speaker. The typical way to go about it is to start with a good solid-state integrated amp and, most importantly, a good pair of speakers.
As far as big speakers go, you could upgrade today to a big pair of used Klipsch floorstanders for well under $500 and make the earth move. They're not exactly "audiophile"...really they are a "party speaker". But for some reason I think they mate very well with Dead tapes (especially after you've smoked a coupla doobies
)...they have a tonal balance that is reminiscent to me of the Dead sound. Speakers like the KG 5.5 s are beasts and Klipschs are generally so efficient that they don't need a lot of power behind them.
But if you're looking to refine your sound, Klipsch probably won't cut it. You'll probably need to spend at least $800 (used) for a decent set of floorstanders, and at least $300 (used) for a decent-sounding amp with some power. And you could easily drop 5x that in a heartbeat.
A pair of Vandersteen 2Ce Sigs would sound good in a room that size, for $1K used. At that price point you're getting near Von Schweikert range, either the V2 (<$1400 used). Others swear by brands like DefTech, Soliloquy, PSB Audio, B&W and many others.
Also note that as the speakers get more revealing, the limitations of the gear driving them become more pronounced. So if you get some "good" speakers, you'll probably want to upgrade your amplification at the same time. I think a minimum of qual for Vandersteens or Von Schweikerts or the like would be a 100WPC integrated amp from Rotel used for $3-500. You'll need some power to fill that room properly.
In Portland, I'd recommend a stop at Echo Audio for a used grab bag of high end, with lots of tube gear; Fred's Sound of Music if you want to check out Paradigm, Thiel, Rotel and other mainstream mid-fi stuff; Stereotypes Audio has some nice 'budget' (sub-$1K) audiophile electronics, plus JM Labs and Proac speakers; and Chelsea Audio in Beaverton has B&W out the ying-yang. But eventually you'll save money by doing the Audiogon.com shuffle, once you've zeroed in on some choices.
The biggest auditioning task is to determine what type of sound suits you -- kinda like with taping gear. Speakers in particular come in all kinds of flavors. Some are very precise but somewhat cold (e.g. Thiel, B&W), while some are warmer and fuzzier (e.g. Vandersteen, Paradigm). And when you're on a budget, you'll rarely find one speaker that does everything you want it to. Compromises...
The most interesting thing I've learned is that speakers are unpredictable. At Stereotypes Audio, I auditioned JMLabs and Proac. The JMLabs are bouncy and musical, and they sounded great when we listened to "Two Against Nature" by Steely Dan. They were much less impressive when I tossed in a stealthed Beck tape (thanks RobertD). The Proacs, by contrast, did an awesome job with the audience tape, and sounded downright horrible with the tight-as-your-asshole-but-overproduced studio disk. Or maybe I should say, the Proacs highlighted the recording 'flaws' (heavy compression and processing) that made the cheaper speakers sound better.
Above all, when you go listen, bring a wide variety of source material and be mentally prepared to take over the shop.